Acute Respiratory Distress Syndrome

1. Acute Respiratory Distress Syndrome Christopher B. Powe, PhD, ACNP-BC Principle | Global Training Institute

2. Outline Outline • Definition • Causes (Traumatic Examples) • Features • Clinical • Pathological • Radiological • Epidemiology • Pathogenesis • Treatment

3. Definition • First description 1967, Ashbaugh and colleagues • Acute Respiratory Distress • Cyanosis Refractory to Oxygen Therapy • Decreased Lung Compliance • Diffuse Infiltrates evident on Chest Radiograph • Initially called Adult Respiratory Distress Syndrome • Changed to Acute (does occur in children)

4. Definition • 1994 American-European Consensus Conference Committee • Acute Onset • Bilateral Infiltrates on CXR • PAWP < 18 mmHg • Acute Lung Injury: PaO2:FiO2 is > 300 • Acute Respiratory Distress Syndrome: PaO2:FiO2 <200

5. Causes • Common, devastating injury affecting both medical and surgical patients • Can be caused from direct or indirect injury • Sepsis is associated with highest progression • 40% of patient with ARDS also have Sepsis • Multiple predisposing disorders increase risk • Chronic ETOH abuse, Chronic Lung Disease and Low serum pH

6. Lower Extremity Trauma

7. Upper Extremity Trauma

8. Abdominal Trauma

9. Head / Trunk Trauma

10. Clinical Features • Three Stages • Acute (Exudative Changes) • Progression to Fibrosing Alveolitis • Recovery

11. Acute Phase • Clinical • Rapid Respiratory Failure • Refractory Hypoxemia • Bilateral Infiltrates on CXR • Indistinguishable from cardiogenic pulmonary edema • Pathological • Diffuse alveolar damage • Presence of neutrophils, macrophages, erythrocytes, hyaline membrane, and protein rich edema fluid in alveolar spaces, capillary injury and disruption of alveolar epithelium

12. Radiographic and Computed Tomographic (CT) Findings in the Acute, or Exudative, Phase (Panels A and C) and the Fibrosing-Alveolitis Phase (Panels B and D) of Acute Lung Injury and the Acute Respiratory Distress Syndrome Ware, L. B. et al. N Engl J Med 2000;342:1334-1349

13. Findings on Light Microscopy and Electron Microscopy during the Acute Phase (Panels A and D) and the Fibrosing-Alveolitis Phase (Panels B, C, and E) of Acute Lung Injury and the Acute Respiratory Distress Syndrome Ware, L. B. et al. N Engl J Med 2000;342:1334-1349

14. Fibrosing Alveolitis Stage • Clinical • Persistent refractory hypoxemia • Increased alveolar dead space • Further decreased compliance • CT Chest shows diffuse interstitial opacities and bullae • Pathological • Fibrosis occurs with acute/chronic inflammatory cells • Partial resolution of pulmonary edema

15. Recovery Phase • Gradual resolution of hypoxemia and lung compliance • Radiographic abnormalities resolve completely • Histologic resolution of fibrosis not well characterized • Pulmonary function returns to normal

16. Mechanisms Important in the Resolution of Acute Lung Injury and the Acute Respiratory Distress Syndrome Ware, L. B. et al. N Engl J Med 2000;342:1334-1349

17. Epidemiology • National Institutes of Health • Incidence 75 per 100,000 population • Mortality Rates • 40-60% • Majority of deaths attributed to sepsis (40%) • MSOF another common comorbidity • Mortality rates decreased from 60-70% as a result of new ventilator technologies

18. Epidemiology • Factors used to predict mortality risk • Chronic liver disease • Nonpulmonary organ dysfunction • Sepsis • Advanced Age • Initial Indexes of Oxygenation/Ventilation • DO NOT predict outcome • No difference in outcome with P:F of 200/300

19. Epidemiology • Survival Outcomes • Normal pulmonary f(x) return in 6 – 12 mths • Residual impairment of pulmonary mechanics: • Mild restriction • Mild obstruction • Gas exchange abnormalities • Usually asymptomatic

20. Pathogenesis • Acute Phase • Two barriers form Alveolar-capillary membrane • Microvascular endothelium • Alveolar epithelium • Influx of Edema Fluid • Protein rich edema fluid fills alveolar air spaces • Caused by endothelial injury and increased vascular permeability • Degree of alveolar epithelial injury important predictor of outcomes

21. Pathogenesis • Acute Phase • Normal Alveolar Epithelium • Two types of cells • 90% Flat Type I cells – very easily injured • 10% Cuboidal Type II cells – resistant to injury • F(x) surfactant production, ion transport, proliferation and differentiation of type I cell after injury • Primary pathologic condition is: • Loss of epithelial integrity

22. Pathogenesis • Acute Phase – Loss of Epithelial Integrity • Contributes to alveolar flooding • Disruption of epithelial fluid transport • Impairs removal of edema fluid • Reduces production and turnover of surfactant • Leads to septic shock in patients with bacterial pneumonia • Disorganized or insufficient repair leads to fibrosis

23. The Normal Alveolus (Left-Hand Side) and the Injured Alveolus in the Acute Phase of Acute Lung Injury and the Acute Respiratory Distress Syndrome (Right-Hand Side) Ware, L. B. et al. N Engl J Med 2000;342:1334-1349

24. Pathogenesis • Neutrophil-Dependent Lung Injury • Clinical studies suggest neutrophil-mediated injury • Questions whether neutrophilic inflammation is the cause or the result of ARDS • Patients with profound neutropenia develop ARDS • Administration of Granulocyte colony-stimulating factor did not increase incidence of ARDS • Anti-inflammatory agents largely are not effective

25. Pathogenesis • Pro-inflammatory Conditions • Cytokines • Initiate and amplify the inflammatory response • Macrophage inhibitory factor (MIF) produced by anterior pituitary found in high concentrations of BAL • Increases production of proinflammatory cytokines inteliukin-8 and tumor necrosis factor Alpha- and can override glucocorticoid-mediated inhibition of cytokine secretion • Better understanding of biologic cytokine activity is needed

26. Pathogenesis • Ventilator-Induced Lung Injury • Older studies suggest oxygen toxicity • Experimental studies suggest volutrauma and high PEEP pressures may also damage alveolar epithelium • Overdistention/Hyperinflation of alveoli • Repeated collapse and reopening of alveoli may initiates the cascade of proinflammatory cytokines • Traditional volumes of 10 to 15 cc/kg thought to have caused much of the VI Lung Injury

27. Pathogenesis • Other Mechanisms of Injury • Abnormalities of Coagulation System • Abnormalities in Surfactant Production • Gas-exchange Abnormalities

28. Treatment • Supportive care may contribute to recent decline in mortality • Research underlying causes with emergent treatment of: • Sepsis • Pneumonia • Abdominal Infections • Acute Bleeding (trauma) • Catheter-induced sepsis • Prevention of gastric bleeding and thromboembolism

31. Treatment • Mechanical Ventilation • Mortality rates with Tv 12-15 cc/kg = 39.8% • Mortality rates with Tv 6 cc/kg = 22% • Positive End-Expiratory Pressure (PEEP) • Increases functional residual capacity • Recruits collapsed alveoli • Use of PEEP at 8 cm/H20 or more • Prone positioning currently being researched • Not shown to be beneficial

32. Treatment • Fluid and Hemodynamic Management • Animal studies suggest low left atrial pressures correlate with reduction of pulmonary edema • Reasonable Objectives: • Maintain intravascular volumes at lowest levels to maintain perfusion • Use of PA / CVP catheters to monitor hemodynamic status

33. Treatment • Surfactant Therapy • Surfactant-replacement successful in infants • One study showed no effect on oxygenation, duration of mechanical ventilation or survival • Problems with study: • Delivered by aerosol • Only 5% reached distal air spaces • Preparation of surfactant protein-free phospholipid • Current clinical trials • Tracheal installation and bronchoalveolar lavage

34. Treatment • Inhaled Nitrous-Oxide and Other Vasodilators • Potent vasodilator • Does not cause systemic vasodilation • Randomized, double-blind studies • Shown no improvement in duration or mortality rates • Current Research • Sodium nitroprusside, hydralazine, prostaglandin E1, prostracyclin

35. Conclusion • Progress has been made: • Understanding pathogenesis • Epidemiology • New ventilation strategies have decreased mortality by 22% • Large prospective, randomized studies are currently needed

36. Acute Respiratory Distress Syndrome Christopher B. Powe, PhD, ACNP-BC Principle | Global Training Institute